Esters of 9-deoxy-6,9 α-epoxymethano-pg analogs

ABSTRACT

Processes for preparing prostacyclin analogs which are 9-deoxy-6,9-epoxymethano derivatives of prostaglandin F 1 α -type compounds, illustrated, for example, by a compound of the formula ##STR1## wherein ˜ indicates alpha or beta configuration; including the products and intermediates produced therein, said products having pharmacological utility.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a divisional application of Ser. No. 788,145,filed Apr. 19, 1977, now issued as U.S. Pat. No. 4,130,569, on Dec. 19,1978.

The present invention relates to prostaglandin analogs for which theessential material constituting a disclosure therefor is incorporated byreference here from U.S. Pat. No. 4,130,569.

I claim:
 1. A cyclic ether of the formula ##STR2## wherein L is (1) avalence bond, (2) --(CH₂)_(d) -- wherein d is one to 5 inclusive, (3)--(CH₂)_(t) --CF₂ -- wherein t is 2, 3, or 4, (4) --CH₂ CH═CH--A--wherein A is a valence bond or --(CH₂)_(h) -- wherein h is one, 2, or 3,or (5) --CH₂ --0--CH₂ --Y-- wherein Y is a valence bond or --(CH₂)_(k)-- wherein k is one or 2; wherein Q₂ is ##STR3## wherein R₃ is hydrogenor alkyl of one to 4 carbon atoms, inclusive, wherein R₂₁ is ##STR4##wherein R₂₅ is ##STR5## wherein C_(g) H_(2g) is alkylene of one to 9carbon atoms, inclusive, with one to 5 carbon atoms, inclusive, in thechain between --CR₅ R₆ -- and terminal methyl, wherein R₅ and R₆ arehydrogen, alkyl of one to 4 carbon atoms, inclusive, or fluoro, beingthe same or different, with the proviso that one of R₅ and R₆ is fluoroonly when the other is hydrogen or fluoro; ##STR6## wherein R₅ and R₆are as defined above with the proviso that neither R₅ nor R₆ is fluorowhen Z is oxa (--0--); wherein Z represents an oxa atom (--0--) or C_(j)H_(2j) wherein C_(j) H_(2j) is a valence bond or alkylene of one to 9carbon atoms, inclusive, substituted with zero, one, or 2 fluoro, withone to 6 carbon atoms, inclusive between --CR₅ R₆₋₋ and the phenyl ring;wherein T is alkyl of one to 4 carbon atoms, inclusive, fluoro, chloro,trifluoromethyl, or --OR₇ wherein R₇ is alkyl of one to 4 carbon atoms,inclusive, and s is zero, one, 2, or 3, with the proviso that not morethan two T's are other than alkyl and when s is 2 or 3 the T's areeither the same or different; or ##STR7## wherein R₆₁ is (a) cycloalkylof 3 to 10 carbon atoms, inclusive, (b) aralkyl of 7 to 12 carbon atoms,inclusive, (c) phenyl, (d) phenyl substituted with one, 2, or 3 chloroor alkyl of one to 4 carbon atoms, inclusive; ##STR8## wherein R₃₄ isphenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl, p-benzamidophenyl,or 2-naphthyl, and wherein R₃₅ is hydrogen or benzoyl;wherein X is cis-or trans--CH═CH--, --C.tbd.C--, or --CH₂ CH_(2--;) and wherein the wavyline (˜) indicates attachment in cis or trans configuration.
 2. Acompound according to claim 1 wherein X is trans--CH═CH--.
 3. A compoundaccording to claim 2 wherein Q₂ is ##STR9## wherein R₃ is hydrogen,methyl, or ethyl.
 4. A compound according to claim 3 wherein R₂₁ is##STR10##
 5. A compound according to claim 4 wherein L is --(CH₂)_(d) --wherein d is one to 5 inclusive.
 6. A compound according to claim 5wherein R₂₅ is ##STR11##
 7. A compound according to claim 6 wherein##STR12## is n-pentyl.
 8. A compound according to claim 5 wherein R₂₅ is##STR13##
 9. A compound according to claim 8 wherein ##STR14##
 10. Acompound according to claim 8 wherein ##STR15##
 11. A compound accordingto claim 4 wherein L is --(CH₂)_(t) --CF₂ -- wherein t is 2, 3, or 4.12. A compound according to claim 3 wherein R₂₁ is ##STR16##